title: Lipopolysaccharide induces IL-6 production in respiratory syncytial virus-infected airway epithelial cells through the toll-like receptor 4 signaling pathway.
abstract: Respiratory syncytial virus (RSV) is a leading cause of bronchiolitis in young children. Microbial agents such as endotoxin and RSV are implicated in airway inflammation during the development of reactive airway disease (RAD) later in childhood. Toll-like receptors (TLRs) are involved in an inflammation cascade through pathogen-associated molecular pattern recognition including lipopolysaccharide (LPS) and viral components. In this study, we investigated the expression of TLRs and cytokine-chemokine production profiles of RSV-infected epithelial cells. In live-RSV infected human tracheal epithelial cell line (9HTEo), TLRs 1-10 mRNA levels were up-regulated in a time-dependent manner compared with ultraviolet (UV)-inactivated RSV. RSV was shown to alter TLR4 membrane and cytosolic location in epithelial cells. Stimulating RSV-infected epithelial cells with TLR4 agonist LPS increased synthesis of IL-6, IL-8, and reduced regulated on activation, normal T cell expressed and secreted (RANTES) production. TLR4 neutralizing antibody HTA125 and TLR4-targeting RNA interference experiments revealed that TLR4 signaling pathway played a predominant role in mediating LPS-induced-IL-6 production of RSV infected epithelial cells. Altogether, our studies indicated that TLR4 play a critical role in leading LPS mediated-IL-6 response in RSV infected-epithelial cells and might be an important factor influencing the cytokine-chemokine profile of epithelial cells interacting with virus and endotoxin, which is correlated with phenotypes of RSV diseases.
authors.affiliation: Immunological Laboratory of Children Research Center, Children's Hospital of Chongqing Medical University, Chongqing 400014, People's Republic of China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Xie
authors.forename: Helen K W
authors.initials: HK
authors.lastname: Law
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xi-Qiang
authors.initials: XQ
authors.lastname: Yang
authors.forename: En-Mei
authors.initials: EM
authors.lastname: Liu
mesh_terms: D000906:Antibodies; D002460:Cell Line; D018946:Chemokine CCL5 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D021381:Protein Transport; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D018113:Respiratory Syncytial Virus, Human / Q000472:pathogenicity* / Q000528:radiation effects; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D014132:Trachea / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D015854:Up-Regulation
chemical_list: D000906:Antibodies; C483024:CCL5 protein, human; C508606:CXCL8 protein, human; D018946:Chemokine CCL5; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; C440499:lipopolysaccharide, Escherichia coli O111 B4